Gpr119 agonist

Abstract

A compound represented by the following formula (I) or the formula (II) disclosed in the specification is a GPR119 agonist, and is used as an agent for treating diabetes: wherein one of T 1 , T 2 , T 3 , and T 4 is N, and each of the other three independently is CR 4 or, in the alternative, each of the four independently is CR 4 ; each of R 2 and R 3 is hydrogen or a C 1-8 alkyl group; the double line consisting of a solid line and a broken line means a single or double bond; A is (CH 2 ) m , a bond, or the like; B is (C(R 5 )H) n , a bond, or the like; one of U and V is N, and the other is CR 7 ; W is C or CR 8 ; each of X and Y is a C 1-3 alkylene group, which optionally has a halogen atom, hydroxyl etc.; Z is C(O)OR 9 , C(O)R 10 , or the like.

1 - 38 . (canceled) 
     
     
         39 . A compound having the following formula (I) or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein one of T 1 , T 2 , T 3 , and T 4  is N, and each of the other three independently is CR 4  or, in the alternative, each of T 1 , T 2 , T 3 , and T 4  independently is CR 4 , wherein R 4  is hydrogen, a halogen atom, nitro, cyano, hydroxyl, a C 1-8  alkyl group, a C 1-8  alkoxy group, a C 1-8  alkyl group having one to three halogen atoms, a C 1-8  alkoxy group having one to three halogen atoms, phenoxy, an alkoxycarbonyl group containing a C 1-8  alkoxy group, carboxyl, carbamoyl, an acyl group containing a C 1-8  alkyl group, an alkylaminocarbonyl group containing a C 1-8  alkyl group, a dialkylaminocarbonyl group containing C 2-12  alkyl groups, an alkoxycarbonylmethylcarbonyl group containing a C 1-8  alkoxy group, an alkylsulfonylmethyl group containing a C 1-8  alkyl group, amino, a C 1-8  alkylamino group, a C 2-12  dialkylamino group, a C 1-8  alkylsulfonylamino group, an acylamino group containing a C 1-8  alkyl group, a C 1-8  alkylsulfinyl group, a C 1-8  alkylsulfonyl group, a cycloalkylsulfonyl group containing a three-membered to six-membered ring, sulfamoyl, a C 1-8  alkylaminosulfonyl group, a C 2-12  dialkylaminosulfonyl group, phenylsulfonyl, or a five-membered or six-membered heteroaryl group; 
         each of R 2  and R 3  independently is hydrogen or a C 1-8  alkyl group; 
         the double line consisting of a solid line and a broken line means a single or double bond; 
         A is (CH 2 ) m , C(O), or a bond, wherein m is an integer of 1 to 3; 
         B is (C(R 5 )H) n , S, O, NR 6 , or a bond, wherein n is an integer of 1 to 3, and each of R 5  and R 6  is hydrogen, a C 1-8  alkyl group, or a three-membered to six-membered cycloalkyl group, provided that B is neither S, O, nor NR 6  when A is a bond; 
         one of U and V is N, and the other is CR 7 , wherein R 7  is hydrogen, a halogen atom, hydroxyl, a C 1-8  alkyl group, a C 1-8  alkoxy group, a C 1-8  alkyl group having one to three halogen atoms, or a C 1-8  alkoxy group having one to three halogen atoms; 
         R 1  is hydrogen, a halogen atom, hydroxyl, a C 1-8  alkyl group, a C 1-8  alkoxy group, a C 1-8  alkyl group having one to three halogen atoms, or a C 1-8  alkoxy group having one to three halogen atoms; 
         W is C or CR 8 , wherein R 8  is hydrogen, a halogen atom, hydroxyl, a C 1-8  alkyl group, a C 1-8  alkoxy group, a C 1-8  alkyl group having one to three halogen atoms, or a C 1-8  alkoxy group having one to three halogen atoms; 
         X is a C 1-3  alkylene group, which optionally has a substituent or substituents selected from the group consisting of a halogen atom, hydroxyl, a C 1-8  alkyl group, a C 1-8  alkoxy group, a C 1-8  alkyl group having one to three halogen atoms, and a C 1-8  alkoxy group having one to three halogen atoms, and X may combine to W with a double bond when W is C; 
         Y is a C 1-3  alkylene group, which optionally has a substituent or substituents selected from the group consisting of a halogen atom, hydroxyl, a C 1-8  alkyl group, a C 1-8  alkoxy group, a C 1-8  alkyl group having one to three halogen atoms, and a C 1-8  alkoxy group having one to three halogen atoms; 
         the substituents of X and Y can be combined to form a C 1-3  alkylene group, which optionally has a C 1-8  alkyl group; and 
         Z is C(O)OR 9 , C(O)R 10 , SO 2 R 11 , C(O)NR 12 R 13 , CH 2 C(O)N(R 14 ) (R 15 ), or a five-membered or six-membered heteroaryl group comprising carbon and nitrogen atoms and optionally comprising oxygen or sulfur atom, one of said carbon atoms combining to the nitrogen atom of the neighboring cyclic amine, and said heteroaryl group optionally having a substituent or substituents selected from the group consisting of a halogen atom, a C 1-8  alkyl group, a C 1-8  alkoxy group, a C 1-8  alkyl group having one to three halogen atoms, and a C 1-8  alkoxy group having one to three halogen atoms, wherein each of R 9 , R 10 , R 11 , R 12 , R 13 , R 14 , and R 15  independently is a C 1-8  alkyl group, a C 2-8  alkenyl group, a three-membered to six-membered cycloalkyl group, phenyl, or a C 1-8  alkyl group having phenyl. 
       
     
     
         40 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 39 , wherein each of T 1 , T 2 , T 3 , and T 4  independently is CR 4 . 
     
     
         41 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 39 , wherein T 1  is N, and each of T 2 , T 3 , and T 4  independently is CR 4 . 
     
     
         42 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 39 , wherein R 4  is hydrogen, a halogen atom, a C 1-8  alkyl group, cyano, an alkoxycarbonyl group containing a C 1-8  alkoxy group, a C 1-8  alkylsulfonyl group, sulfamoyl, phenylsulfonyl, or a five-membered or six-membered heteroaryl group. 
     
     
         43 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 39 , wherein one of CR 4  represented by T 1 , T 2 , T 3 , and T 4  is C—(C 1-8  alkylsulfonyl). 
     
     
         44 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 39 , wherein one of CR 4  represented by T 1 , T 2 , T 3 , and T 4  is C—(C 1-8  alkylsulfonyl), and each of the others of CR 4  is selected from CH, C—(C 1-8  alkyl), or C-(halogeno). 
     
     
         45 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 39 , wherein one of CR 4  represented by T 1 , T 2 , T 3 , and T 4  is C-(1-tetrazolyl) or C-(1,2,4-triazol-1-yl). 
     
     
         46 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 39 , wherein one of CR 4  represented by T 1 , T 2 , T 3 , and T 4  is C-(1-tetrazolyl) or C-(1,2,4-triazol-1-yl), and each of the others of CR 4  is selected from CH, C—(C 1-8  alkyl), or C-(halogeno). 
     
     
         47 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 39 , wherein each of R 2  and R 3  is hydrogen. 
     
     
         48 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 39 , wherein A is CH 2 , and B is a bond. 
     
     
         49 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 39 , wherein U is CH, and V is N. 
     
     
         50 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 39 , wherein U is N, and V is CH. 
     
     
         51 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 39 , wherein each of X and Y is ethylene. 
     
     
         52 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 39 , wherein W is C, and X combines to W with a double bond. 
     
     
         53 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 39 , wherein Z is C(O)OR 9 . 
     
     
         54 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 53 , wherein R 9  is a C 1-8  alkyl group. 
     
     
         55 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 39 , wherein Z is 3-C 1-8  alkyl-1,2,4-oxadiazol-5-yl or 5-C 1-8  alkyl-1,2,4-oxadiazol-3-yl. 
     
     
         56 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 39 , wherein Z is 5-C 1-8  alkylpyrimidin-2-yl. 
     
     
         57 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 39 , wherein each of R 1  and R 7  is hydrogen. 
     
     
         58 . A compound having the following formula (II) or a pharmaceutically acceptable salt thereof: 
       
         
           
           
               
               
           
         
         wherein each of R 21 , R 22 , and R 23  independently is hydrogen, a halogen atom, nitro, cyano, hydroxyl, a C 1-8  alkyl group, a C 1-8  alkoxy group, a C 1-8  alkyl group having one to three halogen atoms, a C 1-8  alkoxy group having one to three halogen atoms, phenoxy, an alkoxycarbonyl group containing a C 1-8  alkoxy group, carboxyl, carbamoyl, an acyl group containing a C 1-8  alkyl group, an alkylaminocarbonyl group containing a C 1-8  alkyl group, a dialkylaminocarbonyl group containing C 2-12  alkyl groups, an alkoxycarbonylmethylcarbonyl group containing a C 1-8  alkoxy group, an alkylsulfonylmethyl group containing a C 1-8  alkyl group, amino, a C 1-8  alkylamino group, a C 2-12  dialkylamino group, a C 1-8  alkylsulfonylamino group, an acylamino group containing a C 1-8  alkyl group, a C 1-8  alkylsulfinyl group, a C 1-8  alkylsulfonyl group, a cycloalkylsulfonyl group containing a three-membered to six-membered ring, sulfamoyl, a C 1-8  alkylaminosulfonyl group, a C 2-12  dialkylaminosulfonyl group, phenylsulfonyl, or a five-membered or six-membered heteroaryl group; 
         Q is N or CH; 
         A 0  is (CH 2 ) p , C(O), S, O, NR 24 , or a bond, wherein p is an integer of 1 to 3, and R 24  is hydrogen, a C 1-8  alkyl group, or a three-membered to six-membered cycloalkyl group; 
         B 0  is (C(R 25 )H) q , O, NR 26 , or a bond, wherein q is an integer of 1 to 3, and each of R 25  and R 26  is hydrogen, a C 1-8  alkyl group, or a three-membered to six-membered cycloalkyl group, provided that B 0  is neither O nor NR 26  when A 0  is S, O, or NR 24 , and that B 0  is not a bond when A 0  is a bond; 
         one of U 0  and V 0  is N and the other is CR 27 , wherein R 27  is hydrogen, a halogen atom, hydroxyl, a C 1-8  alkyl group, a C 1-8  alkoxy group, a C 1-8  alkyl group having one to three halogen atoms, or a C 1-8  alkoxy group having one to three halogen atoms; 
         R 20  is hydrogen, a halogen atom, hydroxyl, a C 1-8  alkyl group, a C 1-8  alkoxy group, a C 1-8  alkyl group having one to three halogen atoms, or a C 1-8  alkoxy group having one to three halogen atoms; 
         W 0  is C or CR 28 , wherein R 28  is hydrogen, a halogen atom, hydroxyl, a C 1-8  alkyl group, a C 1-8  alkoxy group, a C 1-8  alkyl group having one to three halogen atoms, or a C 1-8  alkoxy group having one to three halogen atoms; 
         X 0  is a C 1-3  alkylene group, which optionally has a substituent or substituents selected from the group consisting of a halogen atom, hydroxyl, a C 1-8  alkyl group, a C 1-8  alkoxy group, a C 1-8  alkyl group having one to three halogen atoms, and a C 1-8  alkoxy group having one to three halogen atoms, and X 0  may combine to W 0  with a double bond when W 0  is C; 
         Y 0  is a C 1-3  alkylene group, which optionally has a substituent or substituents selected from the group consisting of a halogen atom, hydroxyl, a C 1-8  alkyl group, a C 1-8  alkoxy group, a C 1-8  alkyl group having one to three halogen atoms, and a C 1-8  alkoxy group having one to three halogen atoms; 
         the substituents of X 0  and Y 0  can be combined to form a C 1-3  alkylene group, which optionally has a C 1-8  alkyl group; and 
         Z 0  is C(O)OR 29 , C(O)R 30 , SO 2 R 31 , C(O)NR 32 R 33 , CH 2 C(O)N(R 34 ) (R 35 ), or a five-membered or six-membered heteroaryl group comprising carbon and nitrogen atoms and optionally comprising oxygen or sulfur atom, one of said carbon atoms combining to the nitrogen atom of the neighboring cyclic amine, and said heteroaryl group optionally having a substituent or substituents selected from the group consisting of a halogen atom, a C 1-8  alkyl group, a C 1-8  alkoxy group, a C 1-8  alkyl group having one to three halogen atoms, and a C 1-8  alkoxy group having one to three halogen atoms, wherein each of R 29 , R 30 , R 31 , R 32 , R 33 , R 34 , and R 35  independently is a C 1-8  alkyl group, a C 2-8  alkenyl group, a three-membered to six-membered cycloalkyl group, phenyl, or a C 1-8  alkyl group having phenyl. 
       
     
     
         59 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 58 , wherein Q is CH. 
     
     
         60 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 58 , wherein each of R 21 , R 22 , and R 23  independently is hydrogen, a halogen atom, a C 1-8  alkyl group, cyano, an alkoxycarbonyl group containing a C 1-8  alkoxy group, a C 1-8  alkylsulfonyl group, sulfamoyl, phenylsulfonyl, or a five-membered or six-membered heteroaryl group. 
     
     
         61 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 58 , wherein one of R 21 , R 22 , and R 23  is a C 1-8  alkylsulfonyl group. 
     
     
         62 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 58 , wherein one of R 21 , R 22 , and R 23  is a C 1-8  alkylsulfonyl group, and each of the others is selected from hydrogen, a C 1-8  alkyl group, or a halogen atom. 
     
     
         63 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 58 , wherein one of R 21 , R 22 , and R 23  is 1-tetrazolyl or 1,2,4-triazol-1-yl. 
     
     
         64 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 58 , wherein one of R 21 , R 22 , and R 23  is 1-tetrazolyl or 1,2,4-triazol-1-yl, and each of the others is selected from hydrogen, a C 1-8  alkyl group, or a halogen atom. 
     
     
         65 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 58 , wherein A 0  is O, and B 0  is CH 2 . 
     
     
         66 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 58 , wherein U 0  is CH, and V 0  is N. 
     
     
         67 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 58 , wherein U 0  is N, and V is CH. 
     
     
         68 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 58 , wherein each of X 0  and Y 0  is ethylene. 
     
     
         69 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 58 , wherein W 0  is C, and X 0  combines to W 0  with a double bond. 
     
     
         70 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 58 , wherein Z 0  is C(O)OR 29 . 
     
     
         71 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 70 , wherein R 29  is a C 1-8  alkyl group. 
     
     
         72 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 58 , wherein Z 0  is 3-C 1-8  alkyl-1,2,4-oxadiazol-5-yl or 5-C 1-8  alkyl-1,2,4-oxadiazol-3-yl. 
     
     
         73 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 58 , wherein Z 0  is 5-C 1-8  alkylpyrimidin-2-yl. 
     
     
         74 . A compound or a pharmaceutically acceptable salt thereof defined in  claim 58 , wherein each of R 20  and R 27  is hydrogen. 
     
     
         75 . An agent for treating diabetes containing a compound or a pharmaceutically acceptable salt thereof defined in  claim 39  as an active ingredient. 
     
     
         76 . A GPR119 agonist containing a compound or a pharmaceutically acceptable salt thereof defined in  claim 39  as an active ingredient. 
     
     
         77 . An agent for treating diabetes containing a compound or a pharmaceutically acceptable salt thereof defined in  claim 58  as an active ingredient. 
     
     
         78 . A GPR119 agonist containing a compound or a pharmaceutically acceptable salt thereof defined in  claim 58  as an active ingredient.